Game Theory of Tumor–Stroma Interactions in Multiple Myeloma: Effect of Nonlinear Benefits

Cancer cells and stromal cells often exchange growth factors with paracrine effects that promote cell growth: a form of cooperation that can be studied by evolutionary game theory. Previous models have assumed that interactions between cells are pairwise or that the benefit of a growth factor is a linear function of its concentration. Diffusible factors, however, affect multiple cells and generally have nonlinear effects, and these differences are known to have important consequences for evolutionary dynamics. Here, we study tumor–stroma paracrine signaling using a model with multiplayer collective interactions in which growth factors have nonlinear effects. We use multiple myeloma as an example, modelling interactions between malignant plasma cells, osteoblasts, and osteoclasts. Nonlinear benefits can lead to results not observed in linear models, including internal mixed stable equilibria and cyclical dynamics. Models with linear effects, therefore, do not lead to a meaningful characterization of the dynamics of tumor–stroma interactions. To understand the dynamics and the effect of therapies it is necessary to estimate the shape of the benefit functions experimentally and parametrize models based on these functions

Who decides what and why: Deciphering Iowa county zoning policies, professionals and politicians

Administrators find themselves in a policy space when they have to balance their professional knowledge of an ambiguous policy with political influence and local implementation history. The Iowa Agricultural Exemption to County Zoning provides an example of administrators making decisions in such a space. This policy exempts from county zoning regulation “land, farm houses, farm barns, farm outbuildings, or other buildings or structures which are primarily adapted by reason of nature and area, for use for agricultural purposes, while so used” (Iowa Code, Chapter 335). Limited guidance from state courts and state legislature leave county zoning administrators in a position of having to muddle through a policy space. In addition to their knowledge of the exemption, this policy space also provides county zoning board of supervisors, citizens and other actors the opportunity to either implicitly or explicitly influence how decisions regarding the exemption are made. This study evaluated where administrators are in this policy space by sending a survey to county zoning administrators across the state to learn what factors influence their administration of this policy. Descriptive and inferential statistics, as well as qualitative analysis were used to analyze the data. Results show that administrators are generally knowledgeable about the policy and because of their role as experts, many administrators do not perceive high levels of political influence. However, administrators in urban counties were found to have a higher level of understanding of how to apply the exemption, but also are subject to higher levels of political influence. These findings are important because the knowledge of, and political influence on the interpretation of the agricultural exemption can potentially act as a barrier to local food systems in Iowa

Exploring Extension Agents\u27 Understandings of Local and Resilient Food Systems

Currently, there is a focus on bolstering local food systems to support overall food system resilience. Local and resilient food systems, though related, are distinct concepts. Their use in food system development is complicated by varying interpretations. Data from a survey of North Carolina Extension agents, a group of food system practitioners, identified a range of definitions of these terms. The results underscore the complex landscape of local food system development and identify a need to build on conceptual understandings within the Extension community and establish shared understandings within food system development efforts

Smad-dependent mechanisms of inflammatory bone destruction

Homeostatic bone remodelling becomes disturbed in a variety of pathologic conditions that affect the skeleton, including inflammatory diseases. Rheumatoid arthritis is the prototype of an inflammatory arthritis characterised by chronic inflammation, progressive cartilage destruction and focal bone erosions and is a prime example for a disease with disturbed bone homeostasis. The inflammatory milieu favours the recruitment and activation of osteoclasts, which have been found to be the cells that are primarily responsible for bone erosions in many animal models of inflammatory arthritis. Among the inflammatory modulators, members of the transforming growth factor (TGF)-β super family are shown to be important regulators in osteoclastogenesis with Smad-mediated signalling being crucial for inducing osteoclast differentiation. These findings have opened a new field for exploring mechanisms of osteoclast differentiation under inflammatory conditions. Recent studies have shown that the TGF-β superfamily members TGF-β1, myostatin and activin A directly regulate osteoclast differentiation through mechanisms that depend on the RANKL–RANK interplay. These growth factors transduce their signals through type I and II receptor serine/threonine kinases, thereby activating the Smad pathway. In this review, we describe the impact of inflammation-induced Smad signalling in osteoclast development and subsequently bone erosion in rheumatoid arthritis

Development of Multigene Expression Signature Maps at the Protein Level from Digitized Immunohistochemistry Slides

Molecular classification of diseases based on multigene expression signatures is increasingly used for diagnosis, prognosis, and prediction of response to therapy. Immunohistochemistry (IHC) is an optimal method for validating expression signatures obtained using high-throughput genomics techniques since IHC allows a pathologist to examine gene expression at the protein level within the context of histologically interpretable tissue sections. Additionally, validated IHC assays may be readily implemented as clinical tests since IHC is performed on routinely processed clinical tissue samples. However, methods have not been available for automated n-gene expression profiling at the protein level using IHC data. We have developed methods to compute expression level maps (signature maps) of multiple genes from IHC data digitized on a commercial whole slide imaging system. Areas of cancer for these expression level maps are defined by a pathologist on adjacent, co-registered H&E slides, allowing assessment of IHC statistics and heterogeneity within the diseased tissue. This novel way of representing multiple IHC assays as signature maps will allow the development of n-gene expression profiling databases in three dimensions throughout virtual whole organ reconstructions

Lettuce Learn: Student Reflections on Building and Sustaining a Community Donation Garden

This article emerged from conversations that we and fellow graduate students have had in building a community donation garden. We created the garden with a vision of enacting food justice in our community, but over the past four years we have experienced complexities with our vision. In this article, we share the complexities with which we have wrestled, how we have encouraged thoughtful dialogue among fellow scholars about these shortcomings and the intricate workings of the agrifood system, and the lessons we have learned through these experiences as early-career scholar-activists. This article represents our collective and individual voices as graduate student garden leaders reflecting on: (a) the ways in which we strived to integrate social justice into our local emergency food system; (b) the paradox of industrial commodity-oriented production agriculture designed to “feed the world,” which neglects the production of healthy food that is locally produced and locally accessible; and (c) the holistic learning approach of combining academic studies with praxis. As students cycle through the graduate program, the garden and partnerships continue, and students take the lessons that they learn through this engagement into their careers and other activities